1. Field of the Invention
This invention relates to novel phthalazone derivatives and more particularly to compounds of the formula ##STR2## wherein R.sup.4 represents a carbamoyl (--CONH.sub.2) group, a dialkylaminoalkylcarbamoyl group, a hydroxyalkylcarbamoyl [--CONH(alkyl)OH] group, an alkylidenehydrazinocarbonyl [--CONHN.dbd.C(alkyl).sub.2 ] group, a hydrazinocarbonyl (--CONHNH.sub.2) group, an alkylhydrazinocarbonyl (--CONHNHalkyl) group, a formyl (--CHO) group, a hydrazonomethyl(--CH.dbd.NNH.sub.2) group, an alkylhydrazonomethyl [--CH.dbd.NNH(alkyl)] group, a hydroxyiminomethyl (--CH.dbd.NOH) group, a dialkylhydrazonomethyl [--CH.dbd.NN-(alkyl).sub.2 ] group, a carbamoylhydrazonomethyl (--CH.dbd.NNHCONH.sub.2) group, or an alkylidenehydrazonomethyl [--CH.dbd.N--N.dbd.C(alkyl).sub.2 ] group; R.sup.6, R.sup.7 and R.sup.8 each represent an alkyl group.
2. Description of the Prior Art
Since thromboxane A.sub.2 was found by Dr. Samuelsson et al in 1974, it has been made clear that the substance is biosynthesized from prostaglandin endoperoxide (PGG.sub.2 or PGH.sub.2) by the action of an enzyme present in the platelets and thromboxane A.sub.2 plays an important role on the subsistence of life in living body.
Thromboxane A.sub.2 is regarded as one of the "local hormone" which appears at injured part in living body and the substance induces contraction of the blood vessels and aggregation of the platelets. Furthermore, it inhibits release of lipids such as cholesterol from the fat cells as well, and an assumption has been made as to thromboxane A.sub.2 that the action is induced as a result of the decrease in C-AMP (adenosine cyclic monophosphate) concentration in the cells with thromboxane A.sub.2. The intensity of these effects reaches as high as several hundred-fold of that led to with prostaglandin. These effects caused with thromboxane A.sub.2 are supposed to be the cause of cerebral apoplexies (cerebral hemorrhage, cerebral thrombosis, etc.) myocardial infarction and as the main risk factor of arteriosclerosis. One of the present inventors has also confirmed that the intracarotid or intracoronary injection of thromboxane A.sub.2 actually induces the experimental stroke or fatal or non-fatal myocardial infarction, respectively.
On the basis of the above supposition, the present inventors investigated to find thromboxane A.sub.2 antagonist and reported on Proceedings of the Japan Academy, Vol. 52, No. 10 pages 591-594 (1976) that phthalazinol (6,8-dimethyl-7-ethoxycarbonyl-4-hydroxymethyl-1-phthalazone, EG-626) was effective. However, in order to get enough blood concentration, phthalazinol has to be given in a large dose, so that it is not yet satisfactory.